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排序方式： 共有586条查询结果，搜索用时 15 毫秒
531.
Zhengchao Ji Tingting Li Xin Zhao Wei Ma Yanyan Li Jing Huang 《Molecules (Basel, Switzerland)》2022,27(17)
A sensitive and rapid bioanalytical method based on the LC-triple-stage fragmentation (LC-MS3) strategy on a hybrid triple quadrupole-linear ion trap mass spectrometer in combination with protein precipitation extraction for sample pretreatment has been developed and validated for the simultaneous determination of the antiepileptic drug oxcarbazepine (OXC) and its main active metabolite (MHD) in human serum. The separation was performed on a Waters XBridge BEH C18 column (2.5 µm, 2.1 × 50 mm) in isocratic elution with 0.1% formic acid in water and methanol (50:50, v:v) as the mobile phase. The run time for each sample was 2.0 min. The calibration curves ranging from 25 to 1600 ng/mL for OXC and from 0.5 to 32 μg/mL for MHD showed correlation coefficients (r) better than 0.99. All of the validation data, such as precision, accuracy and other parameters, fit the requirements of the current bioanalytical method validation guidelines. The LC-MS3 method for quantitation of OXC and MHD was compared with the LC-MRM based method. Passing–Bablok regression coefficients and Bland–Altman plots showed that the developed LC–MS3 method is a reliable method for quantitative analysis of OXC and MHD. The proposed LC-MS3 method was successfully applied to determine the serum concentrations of OXC and MHD to support a clinical study. 相似文献
532.
Peptidyl mono-fluoromethyl ketones (FMKs) are a class of biologically active molecules that show potential as both protease inhibitors for the treatment of a range of diseases and as chemical probes for the interrogation of cellular processes. This review describes the current solid- and solution-phase routes employed for the synthesis of peptidyl mono-FMKs. In addition, it provides a brief overview of some of the key applications of FMKs in the fields of chemical biology and medicinal chemistry. 相似文献
533.
Christoph Dorn Selina Schießer Beatrix Wulkersdorfer Florian Hitzenbichler Martin G. Kees Markus Zeitlinger 《Biomedical chromatography : BMC》2020,34(6):e4820
Pharmacokinetic/pharmacodynamic indices of anti-infective drugs should be referenced to free drug concentrations. In the present study, clindamycin, flucloxacillin and tedizolid have been determined in human plasma by HPLC–UV. The drugs were separated isocratically within 3–6 min on a C18 column using mixtures of phosphate buffer–acetonitrile of pH 7.1–7.2. Sample treatment for the determination of total drug concentrations in plasma included extraction/back-extraction (clindamycin) or protein precipitation (flucloxacillin, tedizolid). The free drug concentrations were determined after ultrafiltration. An ultrafiltration device with a membrane consisting of regenerated cellulose proved to be suitable for all drugs. Maintaining a physiological pH was crucial for clindamycin, whereas maintaining body temperature was essential for tedizolid. The methods were applied to the analysis of total and free drug concentrations in clinical samples and were sufficiently sensitive for pharmacokinetic studies and therapeutic drug monitoring. 相似文献
534.
Thaís Luise Dillenburg Weiss Carolina Mesquita Furtado Marina Venzon Antunes Gustavo Gössling Gilberto Schwartsmann Rafael Linden Simone Gasparin Verza 《Biomedical chromatography : BMC》2020,34(11):e4947
Abiraterone acetate efficacy against prostate cancer is dependent on the circulating levels of abiraterone and its active metabolites, which present significant pharmacokinetic variability among patients. Thus, therapeutic drug monitoring can be performed to improve treatment outcomes. To support such studies, there are only a limited number of bioanalytical methods in current literature. This work presents a fast method to quantify abiraterone and D4A in plasma in 4 min by UPLC–MS/MS. Bioanalytical method validation was performed according to the recommendations of the US Food and Drug Administration. The method was linear within the range of 1–400 ng/ml for abiraterone and 0.2–20 ng/ml for D4A (r2 > 0.99). Based on the analysis of quality control samples at the lower limit of quantification, low, medium and high concentrations, the method was precise (CVabiraterone ≤ 9.72%; CVD4A ≤ 14.64%) and accurate (CVabiraterone 95.51–107.59%; CVD4A 98.04–99.89%). Application of the method to the quantification of abiraterone and D4A in 10 clinical samples revealed important variability in the conversion ratio of abiraterone to D4A (CV 90.85%). Considering the current literature, this is the fastest method to quantify abiraterone and D4A in plasma, allowing for optimization of the analytical routine. 相似文献
535.
Mati Ullah;Muhammad Ijaz Shah;Muhammad Waqqas Hasan;Muhammad Jamshed;Uswa Mustafa;Muhammad Inam; 《中国化学会会志》2024,71(11):1358-1367
Metal nanoparticles (NPs) have emerged as crucial components in precision drug delivery, presenting innovative opportunities to significantly enhance therapeutic efficacy and targeting accuracy. This review investigates recent developments in the engineering of metal NPs, emphasizing their distinctive properties and novel applications in drug delivery systems. A comprehensive analysis is performed on gold, silver, iron, and zinc oxide NPs, emphasizing their exceptional physicochemical properties and enhanced drug-loading capacities. These features collectively enable the development and implementation of targeted and controlled drug delivery systems, indicating a new era of advanced therapeutic approaches. This review article accomplishes this by reflecting on the transformative potential of metal NPs, envisioning heightened efficacy, minimized side effects, and improved patient outcomes within the dynamic landscape of drug delivery platforms. 相似文献
536.
《Biomedical chromatography : BMC》2018,32(9)
Therapeutic drug monitoring may be crucial in selected clinical conditions for the management of HIV infection. In recent years, new antiretrovirals have been introduced and in particular elvitegravir (EVG) is now recommended for first‐line and simplification treatment as well as dolutegravir (DTG) and rilpivirine (RPV). The aim of this study was to develop and validate a high‐performance liquid chromatography–ultraviolet (HPLC‐UV) method for determining EVG and new antiretrovirals DTG and RPV in human plasma. Solid‐phase extraction was applied to a 600 μL plasma sample. Chromatographic separation of the three drugs and internal standard was achieved with a gradient of acetonitrile and phosphate buffer on a C18 reverse‐phase analytical column with a 20 min analytical run time. EVG and DTG were detected at 265 nm and RPV at 290 nm. Mean intra‐ and inter‐day precisions were < 10%; the mean accuracy was <15%. Extraction recovery ranged between 105 and 82% for the drugs analyzed. Calibration curves were optimized according to the expected ranges of drug concentrations in patients; the coefficient of determination was >0.997 for all drugs. This method allows for monitoring EVG, DTG and RPV in the plasma of HIV‐positive patients using HPLC‐UV. 相似文献
537.
Tehreem Tahir Muhammad Ashfaq Muhammad Saleem Muhammad Rafiq Mirza Imran Shahzad Katarzyna Kotwica-Mojzych Mariusz Mojzych 《Molecules (Basel, Switzerland)》2021,26(16)
Synthetic heterocyclic compounds have incredible potential against different diseases; pyridines, phenolic compounds and the derivatives of azo moiety have shown excellent antimicrobial, antiviral, antidiabetic, anti-melanogenic, anti-ulcer, anticancer, anti-mycobacterial, anti-inflammatory, DNA binding and chemosensing activities. In the present review, the above-mentioned activities of the nitrogen-containing heterocyclic compounds (pyridines), hydroxyl (phenols) and azo derivatives are discussed with reference to the minimum inhibitory concentration and structure–activity relationship, which clearly indicate that the presence of nitrogen in the phenyl ring; in addition, the hydroxyl substituent and the incorporation of a diazo group is crucial for the improved efficacies of the compounds in probing different diseases. The comparison was made with the reported drugs and new synthetic derivatives that showed recent therapeutic perspectives made in the last five years. 相似文献
538.
Domain-aware artificial intelligence has been increasingly adopted in recent years to expedite molecular design in various applications, including drug design and discovery. Recent advances in areas such as physics-informed machine learning and reasoning, software engineering, high-end hardware development, and computing infrastructures are providing opportunities to build scalable and explainable AI molecular discovery systems. This could improve a design hypothesis through feedback analysis, data integration that can provide a basis for the introduction of end-to-end automation for compound discovery and optimization, and enable more intelligent searches of chemical space. Several state-of-the-art ML architectures are predominantly and independently used for predicting the properties of small molecules, their high throughput synthesis, and screening, iteratively identifying and optimizing lead therapeutic candidates. However, such deep learning and ML approaches also raise considerable conceptual, technical, scalability, and end-to-end error quantification challenges, as well as skepticism about the current AI hype to build automated tools. To this end, synergistically and intelligently using these individual components along with robust quantum physics-based molecular representation and data generation tools in a closed-loop holds enormous promise for accelerated therapeutic design to critically analyze the opportunities and challenges for their more widespread application. This article aims to identify the most recent technology and breakthrough achieved by each of the components and discusses how such autonomous AI and ML workflows can be integrated to radically accelerate the protein target or disease model-based probe design that can be iteratively validated experimentally. Taken together, this could significantly reduce the timeline for end-to-end therapeutic discovery and optimization upon the arrival of any novel zoonotic transmission event. Our article serves as a guide for medicinal, computational chemistry and biology, analytical chemistry, and the ML community to practice autonomous molecular design in precision medicine and drug discovery. 相似文献
539.
Dongxiao Fan Chenshu Liu Zeling Guo Kan Huang Meixiu Peng Na Li Hengli Luo Tengyao Wang Zhipeng Cen Weikang Cai Lei Gu Sifan Chen Zilun Li 《Molecules (Basel, Switzerland)》2021,26(24)
Critical limb ischemia (CLI) is a severe form of peripheral artery diseases (PAD) and seriously endangers the health of people. Therapeutic angiogenesis represents an important treatment strategy for CLI; various methods have been applied to enhance collateral circulation. However, the current development drug therapy to promote angiogenesis is limited. Resveratrol (RSV), a polyphenol compound extracted from plants, has various properties such as anti-oxidative, anti-inflammatory and anti-cancer effects. Whether RSV exerts protective effects on CLI remains elusive. In the current study, we demonstrated that oral intake of RSV significantly improved hind limb ischemia in mice, and increased the expression of phosphorylated Forkhead box class-O1 (FoxO1). RSV treatment in human umbilical vein endothelial cells (HUVECs) could increase the phosphorylation of FoxO1 and its cytoplasmic re-localization to promote angiogenesis. Then we manipulated FoxO1 in HUVECs to further verify that the effect of RSV on angiogenesis is in a FoxO1-dependent manner. Furthermore, we performed metabolomics to screen the metabolic pathways altered upon RSV intervention. We found that the pathways of pyrimidine metabolism, purine metabolism, as well as alanine, aspartate and glutamate metabolism, were highly correlated with the beneficial effects of RSV on the ischemic muscle. This study provides a novel direction for the medical therapy to CLI. 相似文献
540.
Gellrt Balzs Karvaly Istvn Vincze Istvn Kardi Barna Vsrhelyi Andrs Zsry 《Molecules (Basel, Switzerland)》2021,26(5)
The antihyerlipidemic drug atorvastatin (ATR) is used worldwide as part of the strategy to prevent cardiovascular events. The high prevalence of patient nonadherence remains an important challenge which could be addressed efficiently by precision pharmacotherapy based on therapeutic drug monitoring (TDM). ATR is metabolized to pharmacologically active metabolites, and evidence shows that the sums of ATR acid and lactone form concentrations (ATR + ATRL), or of ATR and hydroxylated metabolites (ATR + MET) should be assayed. A method is presented for the analysis of these substances in serum. Method validation included the estimation of the quantitative relationship between the concentrations and the standard deviations (SD), which supports the optimal incorporation of TDM results into nonparametric pharmacokinetic models. The concentrations of the analytes were evaluated in human subjects receiving ATR. The method’s performance improved by taking the sums of acid and lactone concentrations into account. The concentration–SD relationship was linear, and we recommend applying Theil’s regression for estimating the assay error. All analytes could be detected by 2 h post dose in the samples of human subjects. The changes in metabolite/parent drug concentration ratios in time depended on the dose. The method is suitable for the TDM of ATR with a focus on precision pharmacotherapy. 相似文献